The present invention relates generally to the manufacture, storage, and creation of solutions. More specifically, in an embodiment, the present invention relates to the manufacture, storage, and creation of medical solutions that are administered to patients.
It is known in treating a variety of disease states, and even in order to maintain the health of a mammal, to administer a medical solution. These medical solutions can be administered either enterally, parenterally, or through the peritoneum. Examples of such solutions include medicaments and pharmaceuticals, nutritional formulations, and dialysis solutions. Especially with respect to solutions that are administered intravenously or through the peritoneum, the pH of the solution is an especially important factor. If the pH of the solution is not substantially similar to the physiological pH difficulties can be encountered.
It is known, for example, to use dialysis to support a patient whose renal function has decreased to the point where the kidneys no longer sufficiently function. Two principal dialysis methods are utilized: hemodialysis; and peritoneal dialysis.
In hemodialysis, the patient's blood is passed through an artificial kidney dialysis machine. A membrane in the machine acts as an artificial kidney for cleansing the blood.
In peritoneal dialysis, the patient's own peritoneum is used as a semi-permeable membrane. The peritoneum is the membranous lining in the body cavity that, due to its large number of blood vessels and capillaries, is capable of acting as a natural semi-permeable membrane.
In peritoneal dialysis, a dialysis solution is introduced into the peritoneal cavity utilizing a catheter. After a sufficient period of time, an exchange of solutes between the dialysate and the blood is achieved. Fluid removal is achieved by providing a suitable osmotic gradient from the blood to the dialysate to permit water outflow from the blood. This allows a proper acid-base electrolyte and fluid balance to be returned to the blood. The dialysis solution is simply drained from the body cavity through the catheter.
In order to create an osmotic gradient, the dialysis solution includes an osmotic agent. Although a variety of osmotic agents have been used and considered, typical dialysis solutions include dextrose as an osmotic agent.
It is known in dialysis solutions to also use a buffer. Common buffers used in dialysis solutions are bicarbonate, lactate, and acetate. While initially bicarbonate was the primary buffer considered for use in dialysis solutions, over time, lactate and acetate have been substituted for bicarbonate. This was due to the difficulty in the preparation of bicarbonate-buffered solutions. Lactate and acetate buffers were found to provide greater stability in use over the previous bicarbonate-buffered solutions. See European Patent Application No. 90109963.0.
However, bicarbonate ions provide advantages over lactate or acetate ions. Additionally, experiments indicate that patients exhibit a better tolerance for bicarbonate dialysis solutions. Indeed, certain treatments may require sterile dialysis solutions containing bicarbonate. For example, patients suffering from hypotension and lactate acidosis should receive a bicarbonate-buffered dialysis solution. See, T. S. Ing. et al, "Bicarbonate-Buffered Peritoneal Dialysis", The International Journal of Artificial Organs, Vol. 8, No. 3, p. 121 (1985).
Although bicarbonate functions as a buffer, certain issues are raised when using same. In solution bicarbonate is at equilibrium with CO.sub.2 gas which easily escapes from the solution. When CO.sub.2 gas escapes from the solution, carbonate is generated and the pH of the solution increases.
To avoid this phenomenon, it has been suggested to store bicarbonate in powdered form until just before use. See U.S. Pat. No. 4,489,535. See also European Patent Application No. 0278100 for machine control dialysis.
Alternatively, an impermeable barrier has been proposed to protect the solution. Likewise, methods and containers have been developed for the stabilization of bicarbonate solutions. See U.S. Pat. No. 5,383,324 entitled: "METHOD FOR MANUFACTURING AND STORING STABLE BICARBONATE SOLUTIONS", filed on Apr. 23, 1993.
An additional issue is that in dialysis solutions, dextrose is typically utilized as an osmotic agent. However, like other medical solutions, dialysis solutions must be sterilized before they are administered to a patient. Dextrose, unless it is maintained at an acidic pH, when sterilized, will caramelize. But, on the other hand, bicarbonate must be maintained at a basic pH.
Accordingly, in the art, many attempts have been made to segregate bicarbonate and dextrose so that the two solutions can be maintained at proper pHs when sterilized, e.g., one at a basic pH and the other at an acidic pH. See, for example, U.S. Pat. No. 5,431,496 entitled: "MULTIPLE CHAMBER CONTAINER."
The above issue not only exists with respect to dialysis solutions, but other medical solutions, and indeed, even in the food industry. For example, in many solutions, it would be desirable to initially maintain the solution at a low pH for sterilization and then adjust the solution to a higher, more physiological, pH before the solution is infused into a patient.
However, heretofore, no easy method existed for maintaining a single solution at a reduced pH for sterilization and then without the addition of a composition increasing the pH before infusion.